LDL (low-density lipoprotein), a lipoprotein that exists in the plasma, is the main carrier of cholesterol in the human body. This lipoprotein consists of a quasispherical particle composed of a monolayer of phospholipids and cholesterol surrounding a nucleus of neutral lipids, chiefly composed of cholesterol esters and residual triglycerides. This LDL particle is usually found in the plasma associated with a protein molecule called apolipoprotein B.sub.100 (apo B). This molecule is the ligand that will allow the LDL particle to be internalized by the LDL specific receptors located on the cell membrane. After binding to the LDL receptors, the LDL particle is internalized and degraded in lysosomes and its cholesterol is used in several cell processes, such as membrane synthesis. In other words, in order for the LDL particle to be recognized by its specific receptor, the particle must be associated with its linking element, the apo B. Thus, binding to the LDL receptor of the cell requires a stereochemical conformation of the apo B which is bound to the LDL particle. As such, a domain of the apo B molecule binds to the surface of the LDL particle, whereas another domain binds to the LDL specific receptor of the cell. This internalization by receptor-mediated endocytosis, conceivably requires the presence of the entire lipoprotein associated with the apo B molecule, thus not being triggered by the apo B alone.
It is known in the art that in rapidly proliferating malignant cells, the increased need of cholesterol for new membrane synthesis may result in an over expression of the LDL receptors, which allows a greater uptake of the LDL particles by those cells. This increase is expressed in several lineages of cancer diseases, such as acute myeloid leukemia, myeloproliferous diseases, glioma, endometrial carcinoma, carcinoma of the prostate, uterine carcinoma, cancer of the breast, cancer of the gall bladder, cancer of the renal cells and cancer of the lung. Depending on the lineage of the tumor, the number of LDL receptors can be 3 to 100 times increased, whereas normal cells, due to their low number of LDL receptors have nearly "closed gates" for internalization of the LDL particle.
Some kinds of microemulsions and their respective method for preparation have been previously described and are available in the literature (see Ginsburg et al., Journal of Biological Chemistry, 257:8216, 1982 and Reisinger and Atkinsons, Journal of Lipid Research, 31:849, 1990). In the last decade, several investigators suggested the possibility of using native LDL to shuttle antitumor drugs to cells, based on the increased expression of the LDL in certain types of cancer. Although this experiment proved successful, the difficulty in isolating the LDL from the plasma and handling the preparation thereof are serious drawbacks for its use in the treatment and diagnosis of cancer. Therefore, the use of native LDL for the above purposes remain confined to experimental trials. None of the prior art publications have suggested an artificially made protein-free microemulsion, capable of interacting with the LDL specific receptors and being applicable to a method for diagnosing cancer. Further, conventional methods for diagnosing or controlling the evolution of malignant tumors, such as tomography or conventional scintilography, are not capable of detecting the disease in its early stage or when the tumor is rather small in size.